Developmental and anatomical disruption of the hypothalamic control of pituitary function leads to profound endocrine deficiencies responsible for a number of human medical conditions. Our studies will explore the actions of Hedgehog (Hh), a developmental morphogen, as a mediator of endocrine output by the pituitary. In Aim #1 we seek to characterize the response of pituitary endocrine cells to disrupted Hh activity. After performing these experiments in the accessible larval stage of zebrafish we will then identify the actions of disrupted Hh activity in the mature pituitary. The goal of Aim #2 is to characterize the Hh-responsive cells in the ventral hypothalamus that project cellular processes that contact endocrine cells in the pituitary. Aim #3 is to investigate whether Hh signaling is involved in physiological performance by examining whether Hh signaling in the hypothalamus is affected by osmotic stress, and to determine whether altered Hh signaling impacts osmotic homeostasis. Collectively, these studies will provide insight into whether and how Hh acts as a central regulator of pituitary function in vertebrates. An improved understanding of the molecular mechanisms mediating hypothalamic-pituitary connectivity could aid in the diagnosis and treatment of diseases impacting fertility, growth, energy homeostasis, and salt and water balance that are rooted in hypo- or hypersecretion of pituitary hormones. PUBLIC HEALTH RELEVANCE: Developmental and anatomical disruption of the hypothalamic control of pituitary function leads to profound endocrine deficiencies responsible for a number of human medical conditions. Our studies will explore the actions of the secreted protein Hedgehog, a developmental morphogen, as a mediator of endocrine output by the pituitary. To aid in the diagnosis and treatment of diseases impacting fertility, growth, energy homeostasis, and salt and water balance, we aim to provide a better understanding of central pituitary regulation.